CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients

Background: Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there isconsiderable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understandingthe current state of evidence in this area and its limitations is important for the care of patients who requireendocrine therapy for breast cancer. Materials and
Methods: A total of 101 patients with breast cancer whoreceived tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene bynested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poormetabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neustatus, and stage 3.
Results: The mean age of the patients with the disease recurrence was 50.8±6.4 and in nonrecurrent patients was 48.2±6.8. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6%(n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifentreatedpatients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolicvariants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women withbreast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreasedlikelihood of recurrence.
Conclusions: This study for the first time demonstrated significant effects of CYP2D6extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvanttamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor ofbreast cancer outcome in Her2-neu positive women receiving tamoxifen.